Detection of voltage potentials and changes to the internal ionic environment of cells can be useful in monitoring bioactivities of cells. For example, many cells experience significant changes in internal calcium ion (Ca2+) concentration in response to binding of a ligand to a G-protein receptor. In another aspect, certain cells experience large changes in voltage potential across membranes, e.g., in response to contact with neurotransmitters at a synapse. Such cellular changes are responsible for important functions in cells and can be indicative of the health, function, or development processes of the cells.
Chloride is another important ion, particularly for cellular homeostasis. Sodium and potassium ions are moved across cell membranes passively or by an active transport system—the sodium-potassium pump—and chloride ions are actively transported by the chloride ion pump. The chloride ion pump is important for controlling sweat, digestive juices and mucus; and for maintaining cellular homeostasis and blood pH. In cystic fibrosis, a genetic defect results in a misshapen chloride ion pump. Chloride levels within the cells are not controlled properly, and the cells produce thick mucus. Disruption of chloride ions is also implicated in diseases associated with inflammation, and is important for controlling blood pH.
In studying intracellular chloride levels in response to products with treatment potential, signal transduction studies are carried out in cell types that are not representative of the actual cells of interest. For example, researchers may be limited to studying signaling agents and potential therapeutics in rodents or immortal cell lines in vitro, which often provide results not repeated in human cells, or clinical patients. Researchers may create host cells for study by introduction of oncogenes to primary cell lines, e.g., with differentiation to a cell type of choice. However, such host cells or cells generated cannot be relied on to respond normally on contact with bioactive agents.
A need therefor exists for model cell systems representative of cells and tissues existing in live animal systems of interest. It would be desirable to have chloride sensor peptide constructs that can be targeted to specific intracellular locations. Benefits would also be realized if systems were available allowing three dimensional signal detection in mock tissues of representative cells in vitro. These systems would be useful for screening and identifying and confirming efficacy of bioactive agents.